Low levels of plasma protein S, protein C and coagulation factor XII during early pregnancy and adverse pregnancy outcome
Yasuhiko Ebina
1
Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan
,
Masahiro Ieko
2
Department of Internal Medicine, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan
,
Sumiyoshi Naito
3
Department of Clinical Laboratory School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan
,
Gen Kobashi
4
Department of Planning and Management, National Institute of Radiological Sciences, Chiba, Japan
,
Masashi Deguchi
1
Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan
,
Hisanori Minakami
5
Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
,
Tatsuya Atsumi
6
Department of Medicine II, Hokkaido University Graduate School of Medicine, Sapporo, Japan
,
Hideto Yamada
1
Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan
› Author AffiliationsFinancial support: This work was supported in part by a Grant-in-Aid from the Japan Society for the Promotion of Science (Grant No. 26462489, 25462593) and the Ministry of Health, Labour and Welfare of Japan (Grant No. H25-Jisedai-Ippan-005).
It was the study objective to evaluate whether low levels of plasma protein S (PS) activity, free PS, protein C (PC) activity and coagulation factor XII (FXII) during early pregnancy are related to adverse pregnancy outcomes. Peripheral blood samples were obtained at 8–14 gestational weeks (GW) from a consecutive series of 1,220 women. The levels of plasma PS activity, free PS, PC activity, and FXII were measured. Cut-off values were defined as < 1st, < 5th, and < 10th percentiles of values obtained from 933 women whose pregnancies ended in normal deliveries without complications. PS activity of < 10th percentile yielded risks of pregnancy-induced hypertension (PIH) and severe PIH, while free PS level of < 5th percentile yielded a risk of preeclampsia. FXII level of < 1st percentile yielded a risk of premature delivery (PD) at < 34 GW. None was associated with PD at < 37 GW, fetal growth restriction or fetal loss. A multivariate analysis demonstrated that PS activity of < 10th percentile (odds ratio 5.9, 95 % confidence interval 1.7–18.1) and body mass index (BMI) ≥ 25 kg/m2 (4.3, 1.1–13.3) were independent risk factors for severe PIH. Similarly, free PS level of < 5th percentile (4.4, 1.0–14.3) and BMI ≥ 25 kg/m2 (4.0, 1.3–10.9) were independent risk factors for pre-eclampsia. In conclusion, women with low levels of plasma PS activity and free PS during early pregnancy might have increased risks of PIH, severe PIH or pre-eclampsia. Women with low FXII level might have an increased risk of PD at < 34 GW.
Keywords
Factor XII -
pregnancy -
pregnancy-induced hypertension -
premature delivery -
protein C -
protein S
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